To improve the efficiency and efficacy of drug abuse interventions, an understanding of the age-related changes in behavior prevalences, comorbidities, and health disparities, and the evolving role of various risk factors from adolescence through middle adulthood, is crucial. Today there is an unprecedented amount of existing high-quality data that have enormous potential to shed new light on these issues. Many of these data sets are nationally representative, drawn from populations that span a wide range of ages. New methods now exist to tap those data in order to address important, new scientific questions about drug use, abuse, and dependence (drug UAD) from a developmental perspective. To this end, we propose the innovative application of the time-varying effect model (TVEM) to data from two complementary national studies of health risk behaviors: The National Longitudinal Study of Adolescent Health (N=20,745) and the 2012 National Survey on Drug Use and Health (N=63,809). TVEM flexibly estimates behavior prevalences and associations among variables as continuous, flexible functions of age. Specifically, the specific aims for this projec are as follows. (1) To model flexible, age-varying trends in drug UAD from adolescence into middle adulthood. We will estimate rates of alcohol, tobacco, marijuana, and other drug use, abuse and dependence as a complex function of continuous age from ages 12 to 50. Trends will be estimated across sex and race/ethnicity to document age-varying health disparities. (2) To elucidate the age-varying role of mental health problems in the course of drug UAD from adolescence into middle adulthood. We will examine how depressive symptoms and suicidal ideation are differentially associated with drug UAD as a continuous, complex function from ages 12 to 50. (3) To estimate age-varying effects of early and concurrent risk factors on drug UAD from adolescence into middle adulthood. We will examine how and when specific risk and protective factors are associated with drug UAD from ages 12 to 50. We will consider early risk factors at the individual, parent, peer, school, and community levels, as well as concurrent factors such as marriage and parenthood. (4) To examine contributors to health disparities in drug use. To advance understanding of the developmental course of health disparities, we will examine sex and race/ethnicity as moderators of (a) age-varying comorbidities of drug UAD and mental health problems and (b) age-varying associations between risk factors and drug UAD. This project will provide knowledge about the developmental course of drug UAD and related health disparities, allowing prevention scientists and clinicians to design interventions that matc the most promising mechanisms of change to the most appropriate age period within population subgroups. To maximize the project's overall impact, we will actively disseminate this promising new analytic approach to drug abuse researchers.